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Publication Abstract from PubMed

Specific interactions between proteins govern essential physiological processes including signaling. Many enzymes, especially the family of serine/threonine phosphatases (PSPs: PP1, PP2A, and PP2B/calcineurin/CN), recruit substrates and regulatory proteins by binding short linear motifs (SLiMs), short sequences found within intrinsically disordered regions that mediate specific protein-protein interactions. While tremendous progress had been made in identifying where and how SLiMs bind PSPs, especially PP1 and CN, essentially nothing is known about how SLiMs bind PP2A, a validated cancer drug target. Here we describe three structures of a PP2A-SLiM interaction (B56:pS-RepoMan, B56:pS-BubR1, and B56:pSpS-BubR1), show that this PP2A-specific SLiM is defined as LSPIxE, and then use these data to discover scores of likely PP2A regulators and substrates. Together, these data provide a powerful approach not only for dissecting PP2A interaction networks in cells but also for targeting PP2A diseases, such as cancer.

Expanding the PP2A Interactome by Defining a B56-Specific SLiM.,Wang X, Bajaj R, Bollen M, Peti W, Page R Structure. 2016 Dec 6;24(12):2174-2181. doi: 10.1016/j.str.2016.09.010. Epub 2016, Oct 27. PMID:27998540^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.